Triiodothyronine Acts as a Smart Influencer on Hsp90 via a Triiodothyronine Binding Site

Fan, Lu; Warnecke, Athanasia; Weder, Julia; Preller, Matthias; Zeilinger, Carsten

doi:10.3390/ijms23137150

IJMS

2022

DOI: 10.3390/ijms23137150

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Triiodothyronine Acts as a Smart Influencer on Hsp90 via a Triiodothyronine Binding Site

Lu Fan

Athanasia Warnecke

Julia Weder

et al.

Abstract: Microarray-based experiments revealed that thyroid hormone triiodothyronine (T3) enhanced the binding of Cy5-labeled ATP on heat shock protein 90 (Hsp90). By molecular docking experiments with T3 on Hsp90, we identified a T3 binding site (TBS) near the ATP binding site on Hsp90. A synthetic peptide encoding HHHHHHRIKEIVKKHSQFIGYPITLFVEKE derived from the TBS on Hsp90 showed, in MST experiments, the binding of T3 at an EC50 of 50 μM. The binding motif can influence the activity of Hsp90 by hindering ATP accessi… Show more

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2024

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Cited by 2 publications

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Prediction of Treatment Mechanisms of Scutellariae Radix on Viral Pneumonia Through Network Pharmacology: Focus on Hypoxic State Regulation Through HIF-1α and HSP90

Shon,

Han,

Kim

et al. 2024

J Korean Med

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Objectives: In this study, we used network-based systems pharmacology analysis and molecular docking methods to predict the therapeutic mechanism of Scutellariae Radix on viral pneumonia.Methods: We screened active components of Scutellariae Radix and its’ genes by TCMSP. Also, we extracted viral pneumonia related target genes through Gene Cards, CTD and DisGeNet. To construct Protein-protein Interaction, STRING database was used. For functional enrichment, using SRplot platform, genes were classified by 3 categories: cellular component (CC), molecular function (MF) and biological process (BP). Molecular docking was conducted by AutoDockTools (version 4.2.6).Results: 32 Network-based systematic pharmacology analysis identified 37 target genes associated with baicalein. Based on the network and gene ontology analysis of the active ingredient's target genes and disease target genes, we identified nine core genes (AKT1, BAX, BCL2, CASP3, HIF1A, PTGS2, RELA, TP53, VEGFA) and HSP90 as involved. Notably, HIF1A showed the highest relevance, overlapping with two or more utilized programs. Hypoxia-inducible factor 1-alpha (HIF-1α) has been implicated in the expression of inflammatory cytokines, the induction of hypoxia, and the triggering of cytokine storms. Baicalein, a major component of SR, binds to both HIF-1 α and HSP90, suggesting that it may be a possible targeted treatment for viral pneumonia.Conclusions: Baicalein may bind to HIF-1α to control inflammation caused by viral infectious diseases and may also regulate hypoxic conditions to prevent impairment of lung function caused by an overactive immune system. These findings suggest further research into the molecular mechanisms involved in hypoxia and provide a scientific basis for improving the treatment of viral infectious diseases.

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Prediction of Treatment Mechanisms of Scutellariae Radix on Viral Pneumonia Through Network Pharmacology: Focus on Hypoxic State Regulation Through HIF-1α and HSP90

Shon,

Han,

Kim

et al. 2024

J Korean Med

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Acetylome Analyses Provide New Insights into the Effect of Chronic Intermittent Hypoxia on Hypothalamus-Dependent Endocrine Metabolism Impairment

Kong,

Ji,

Zhan

et al. 2024

Biology

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Paediatric obstructive sleep apnoea (OSA) is a highly prevalent sleep disorder resulting in chronic intermittent hypoxia (CIH) that has been linked to metabolism and endocrine impairment. Protein acetylation, which is a frequently occurring posttranslational modification, plays pivotal roles in the regulation of hypothalamic processes. However, the effects of CIH-induced global protein acetylation on hypothalamic function and endocrine metabolism remain poorly understood. To bridge this knowledge gap, we conducted a study utilizing liquid chromatography–mass spectrometry to analyse the lysine acetylome and proteome of the hypothalamus in healthy infantile mice exposed to 3 weeks of intermittent hypoxia (as a CIH model) compared to normoxic mice (as controls). Our analysis identified and quantified 2699 Kac sites in 2453 proteins. These acetylated proteins exhibited disruptions primarily in endocrine metabolism, the citrate cycle (TCA cycle), synapse function, and circadian entrainment. Additionally, we observed significant down-regulation of proteins that are known to be involved in endocrine hormone secretion. This study aimed to elucidate the molecular mechanisms underlying CIH-induced alterations in protein acetylation within the hypothalamus. By providing valuable insights into the pathophysiological processes associated with CIH and their impacts on hypothalamic function, our findings contribute to a deeper understanding of the consequences stemming from CIH-induced changes in protein acetylation within the hypothalamus as well as its potential role in endocrine impairment.

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Triiodothyronine Acts as a Smart Influencer on Hsp90 via a Triiodothyronine Binding Site

Cited by 2 publications

References 22 publications

Prediction of Treatment Mechanisms of Scutellariae Radix on Viral Pneumonia Through Network Pharmacology: Focus on Hypoxic State Regulation Through HIF-1α and HSP90

Prediction of Treatment Mechanisms of Scutellariae Radix on Viral Pneumonia Through Network Pharmacology: Focus on Hypoxic State Regulation Through HIF-1α and HSP90

Acetylome Analyses Provide New Insights into the Effect of Chronic Intermittent Hypoxia on Hypothalamus-Dependent Endocrine Metabolism Impairment

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